FDA Approves Ruxolitinib for Treatment of Chronic GVHD

Nick Mulcahy

September 22, 2021

The US Food and Drug Administration (FDA) has approved ruxolitinib (Jakafi) for treatment of chronic graft-versus-host disease (GVHD) in adults and in pediatric patients 12 years and older who have already had one or two lines of systemic therapy.

The product, a JAK inhibitor first marketed for use in myelofibrosis, is already approved for acute GVHD in adults and pediatric patients over 12 who are steroid refractory.

Both forms of GVHD (acute occurring within 100 days of transplant, and chronic more than 100 days after transplant) are associated with significant morbidity and mortality and can affect multiple organ systems.

The FDA approval, granted to the drug manufacturer Incyte, was based results from the REACH3 study, a phase 3, randomized, open-label, multicenter study of 329 patients comparing ruxolitinib (n = 165) to best available therapy (BAT; n = 164)  for treatment of steroid-refractory, chronic GVHD after allogeneic stem cell transplantation.

The primary endpoint of overall response rate (ORR) at week 24 (which was day 1 of cycle 7) was 49.7% for ruxolitinib compared with 25.6% for BAT (P < .001).

Ruxolitinib led to longer median failure-free survival than BAT (>18.6 months vs. 5.7 months; P < .001) and higher symptom response (24.2% vs. 11%; P = .001).

The most common (≥10% of patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2% in the ruxolitinib group and 10.1% in the BAT group) and anemia (12.7% and 7.6%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two treatment groups, reported investigators.

Results from the REACH3 study — the first multicenter randomized controlled trial for chronic GVHD that is positive — were presented at the American Society of Hematology annual meeting last December and were described as potentially practice changing, as reported by Medscape Medical News at the time. The full results were published in the New England Journal of Medicine in July.

"Nearly half of the people who develop chronic GVHD do not respond adequately to steroids — the current standard of care — making this life-threatening condition particularly challenging to treat," said principal investigator Robert Zeiser, MD, University Medical Center Freiburg, Freiburg, Germany.

"This approval represents a significant advancement in the treatment of appropriate patients with chronic GVHD," said Zeiser in a press release from Incyte.

"In the US, there are over 14,000 people living with chronic GVHD, many of whom face significant complications that may impair daily activities and linger for years,” said Susan Stewart, executive director of the Blood & Marrow Transplant Information Network, a US-based nonprofit. Stewart had a bone marrow transplant nearly four decades ago and said  the new approval is "an important step forward in the treatment of a disease with few options."

The application for ruxolitinib for chronic GHVD was reviewed under the FDA's Priority Review program as well as the Project Orbis program, an FDA initiative that allows for concurrent submission and review of oncology drugs among various international partners.

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